Prostate cancer is the second-most common cancer found in American men. The molecular basis of prostate cancer is complex. Recently efforts have been made to determine genes that are differentially expressed in normal prostate tissues and prostate tumors. One gene that is expressed in normal prostate tissue but consistently absent in prostate cancers encodes TACI, a cell surface receptor that until now has been assumed to be lymphocyte-specific. Recent findings have established that TACI is one of several receptors that can bind to two growth factors, BAFF and APRIL, and is thought to induce apoptosis in lymphocytes. We have determined that both normal prostate tissue and a number of prostate cancer cell lines express APRIL. We propose that APRIL provides an autocrine growth stimulus for normal prostate epithelial cells which is antagonized by TACI-mediated apoptosis. Loss of TACI expression may therefore result in the accumulation of aberrant cells in the prostate which increases the susceptibility to transformation. In the research proposed here we will 1) study the role of TACI and APRIL in the growth of prostate tumor cell lines both in vitro and in a xenograft tumor model and, 2) Study the development of prostate neoplasia in TACI-deficient mice. We anticipate that these studies will establish TACI and APRIL as molecular targets for intervention in the prevention and treatment of prostate cancer.